Intrauterine hypoxia slowing the development of Purkinje cells and reducing the expression of cerebellin in mice

XU Ji-wei YANG Chang-qing CHEN Xiao-ping CHEN Xu-dong FAN Wen-juan

Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (3) : 344-351.

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Acta Anatomica Sinica ›› 2021, Vol. 52 ›› Issue (3) : 344-351. DOI: 10.16098/j.issn.0529-1356.2021.03.003
Neurobiology

 Intrauterine hypoxia slowing the development of Purkinje cells and reducing the expression of cerebellin in mice

  • XU Ji-wei1 YANG Chang-qing2 CHEN Xiao-ping3 CHEN Xu-dong1* FAN Wen-juan1*
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Abstract

Objective  To investigate the effects of the development of Purkinje cells and expression of cerebellin in postnatal mice with intrauterine  hypoxia.    Methods  Twenty healthyice were randomly divided into two groups: control group and hypoxia group, with 10 mice in each group. Mice in the hypoxia group were placed in the hypoxia chamber of the animal since the 14th day of gestation to make an animal model of intrauterine hypoxia. After the mother gave birth, the experimental animals were divided into hypoxia group and control group. There were 6 age groups including postnatal day  (P)0, P5, P9, P14, P21 and P30 in each group, and 5 mice in each age group. The cerebellum tissue was taken for vibrating sectioning. The developmental changes of calbindin-positive Purkinje cells were detected by immunofluorescence technique. The expression of cerebellin in Purkinje cell protuberances was detected by cerebellin (CBLN)1, CBLN4 and calbindin double labeling. Finally, Western blotting was used to semiquantitatively analyze the protein expression of cerebellar peptide in cerebellum at each time point.   Results  Compared with the control group of the same age, the number of cerebellar Purkinje cells in the hypoxic group decreased, the dendritic branches decreased, and the arrangement was disordered, and the expression of CBLN1 and CBLN4 in the cortex were significantly reduced.    Conclusion  Intrauterine hypoxia leads to abnormal development of the cerebellar Purkinje cells and synaptic changes.

Key words

Hypoxia / Cerebellum / Purkinje cell / Cerebellin / Western blotting / Mouse

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XU Ji-wei YANG Chang-qing CHEN Xiao-ping CHEN Xu-dong FAN Wen-juan.  Intrauterine hypoxia slowing the development of Purkinje cells and reducing the expression of cerebellin in mice[J]. Acta Anatomica Sinica. 2021, 52(3): 344-351 https://doi.org/10.16098/j.issn.0529-1356.2021.03.003

References

[1] Ni N. Blood flow monitoring of fetal hypoxia in uterus[J]. World Latest Medicne Information, 2019,19(84):228,233.(in Chinese)
倪娜. 胎儿宫内缺氧的血流监测[J]. 世界最新医学信息文摘, 2019,19(84):228,233.
[2] Lawrence KM, McGovern PE, Mejaddam A, et al. Chronic intrauterine hypoxia alters neurodevelopment in fetal sheep[J]. J Thorac Cardiovasc Surg, 2019,157(5):1982-1991.
[3] Chen XD, Hua XY, Sun DH, et al. Compound porcine cerebroside and ganglioside relieves brain injury and promotes expression of cerebellin 4 in neonatal mice with intrauterine hypoxia[J]. Chinese Journal of Cellular and Molecular Immunology, 2019,35(8):721-726.(in Chinese)
陈旭东, 华新宇, 孙丹华,等. 复方猪脑肽节苷脂减轻宫内缺氧后新生小鼠脑损伤并促进小脑肽4(CBLN4)表达[J]. 细胞与分子免疫学杂志, 2019,35(8):721-726.
[4] Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions[J]. Eur J Neurosci, 2011,33(8):1447-1461.
[5] Yuzaki M. Cbln1 and its family proteins in synapse formation and maintenance[J]. Curr Opin Neurobiol, 2011,21(2):215-220.
[6] Seigneur E, Polepalli JS, Südhof  TC. Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs[J]. Proc Natl Acad Sci USA, 2018,115(43):E10235-E10244.
[7] Zhong C, Shen J, Zhang H, et al. Cbln1 and Cbln4 are structurally similar but differ in GluD2 binding interactions[J]. Cell Rep, 2017,20(10):2328-2340.
[8] Takayasu Y, Shino M, Nikkuni O, et al. Oxygen-glucose deprivation increases firing of unipolar brush cells and enhances spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum[J]. Neurosci Res, 2016,106:1-11.
[9] Zhang Y, Shi Z, Magnus G, et al. Functional circuitry of a unique cerebellar specialization: the valvula cerebelli of a mormyrid fish[J]. Neuroscience, 2011,182:11-31.
[10] Kitamura K, Kano M. Dendritic calcium signaling in cerebellar Purkinje cell[J]. Neural Netw, 2013,47:11-17.
[11] Ito-Ishida A, Okabe S, Yuzaki M. The role of Cbln1 on Purkinje cell synapse formation[J]. Neurosci Res, 2014,83:64-68.
[12] Thornton C, Leaw B, Mallard C, et al. Cell death in the developing brain after hypoxia-ischemia[J]. Front Cell Neurosci, 2017,11:248.
[13] Torres-Cuevas Ⅰ, Corral-Debrinski M, Gressens P. Brain oxidative damage in murine models of neonatal hypoxia/ischemia and reoxygenation[J]. Free Radic Biol Med, 2019,142:3-15.
[14] Chen XD,Yuan L,Fan WJ.Panax notoginseng saponins ameliorate cerebral injury and learning and memory function in neonatal rats with intrauterine hypoxia[J].Chinese Journal of Anatomy,2017,40(2):157-159.(in Chinese)
陈旭东, 袁磊, 范文娟. 三七总皂苷改善宫内缺氧新生鼠脑损伤及学习记忆功能[J]. 解剖学杂志, 2017,40(2):157-159.
[15] Cheng XSh,Du YW,Jiang JY,et al. Neuronal apoptosis in mouse cerebellar cortex development[J].Acta  Anatomica Sinica, 2008,39(4):470-474. (in Chinese)
程相树, 杜耀武, 蒋杞英, 等. 小鼠小脑皮质发育中的神经元凋亡[J]. 解剖学报, 2008,(4):470-474.
[16] Deng JB,Xu XB,Fan WJ. Development and gene regulation of cerebellum[J].Progress of Anatomical Sciences, 2010,16(2):181-186. (in Chinese)
邓锦波, 徐晓波, 范文娟. 小脑发育及其基因调节[J]. 解剖科学进展, 2010, 16 (2): 181-186.
[17] Chen WJ,ZhangWL,Li X,et al. Interaction between cell migration and vasculature in the developing cerebellum of the mouse [J].Acta Anatomica Sinica, 2013,44(6):740-747. (in Chinese)
陈文静, 张文玲, 李雪, 等. 小鼠小脑皮质发育过程中细胞迁移及血管之间的相互作用[J]. 解剖学报, 2013,44(6):740-747.
[18] Raymond M, Li P, Mangin JM, et al. Chronic perinatal hypoxia reduces glutamateaspartate transporter function in astrocytes through the Janus kinase/signal transducer and activator of transcription pathway[J]. J Neurosci, 2011,31(49):17864-17871.
[19] Dallas M, Boycott HE, Atkinson L, et al. Hypoxia suppresses glutamate transport in astrocytes[J]. J Neurosci, 2007,27(15):3946-3955.
[20] Schild L, Reiser G. Oxidative stress is involved in the permeabilization of the inner membrane of brain mitochondria exposed to hypoxia/reoxygenation and low micromolar Ca2+[J]. FEBS J, 2005, 272(14):3593-3601.
[21] Schild  L, Huppelsberg  J, Kahlert S, et al. Brain mitochondria are primed by moderate Ca2+ rise upon hypoxia/reoxygenation for functional breakdown and morphological disintegration[J]. J Biol Chem, 2003,278(28):25454-25460.
[22] Niu BH,Zhang Y,Niu YL,et al.Radial glial cell and development of cerebellar cortex in mouse [J].Acta Anatomica Sinica, 2010,41(4):498-503. (in Chinese)
牛保华, 张艳, 牛艳丽, 等. 小鼠放射状胶质细胞和小脑皮质的发育[J]. 解剖学报, 2010,41(4):498-503.
[23] Yuzaki M. The C1q complement family of synaptic organizers: not just complementary[J]. Curr Opin Neurobiol, 2017,45:9-15.
[24] Rong Y, Bansal PK, Wei P, et al. Glycosylation of Cblns attenuates their receptor binding[J]. Brain Res, 2018,1694:129-139.
[25] Wei P, Pattarini R, Rong Y, et al. The Cbln family of proteins interact with multiple signaling pathways [J]. J Neurochem, 2012,121(5):717-729.
[26] Takeuchi E, Ito-Ishida A, Yuzaki M, et al. Improvement of cerebellar ataxic gait by injecting Cbln1 into the cerebellum of cbln1-null mice[J]. Sci Rep, 2018, 8(1):6184.
[27] Pendyala G, Chou S, Jung Y, et al. Maternal immune activation causes behavioral impairments and altered cerebellar cytokine and synaptic protein expression[J]. Neuropsychopharmacology, 2017, 42(7):1435-1446.
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